Adrenergic receptor subtypes differentially influence acrolein-induced ventilatory, vascular leakage, and inflammatory responses.

Abstract

Adrenergic receptors (AR) are manipulated therapeutically for the treatment of pulmonary and cardiovascular diseases; however, their role in air pollutant-induced respiratory effects is poorly understood. We examined the contribution of AR-subtypes in acrolein-induced respiratory effects through selective receptor inhibition. We pre-treated 12-week-old male Wistar-Kyoto rats intraperitoneally daily for 9-days with subtype-specific AR antagonists prazosin (PRZ, α1-AR antagonist; 2-mg/kg-day), yohimbine (YOH, α2-AR antagonist; 5-mg/kg-day), or propranolol (PROP, β-AR antagonist; 10-mg/kg-day). On day-8 and day-9 of treatment, rats were exposed nose-only to air or acrolein (1.6 or 3.2 ppm), ∼4 h/day. Head-out plethysmography during exposure on Day-9 revealed overall concentration-dependent acrolein-related reduced ventilatory capacity, which was exacerbated in PRZ- and YOH-treated animals. Nasal (NALF) and bronchoalveolar lavage fluid (BALF), and blood samples were collected on day-9. Plasma epinephrine levels did not change; however, corticosterone decreased in YOH- and PROP-treated air-exposed animals. Adrenal and spleen weights were higher in PRZ-treated animals. Acrolein, 3.2-ppm depleted circulating lymphocytes in saline-treated and increased neutrophils in PRZ- and YOH-treated animals. NALF and BALF analysis indicated 3.2-ppm acrolein-induced neutrophilic and lymphocytic inflammation (NALF>BALF), which was exacerbated in lung of PRZ- and YOH-treated rats and slightly dampened in PROP-treated rats. However, acrolein-induced vascular protein leakage and increases in inflammatory cytokines in NALF were reduced by PROP-treatment. In conclusion, this study highlights sympathetically-mediated adrenoreceptor influence on acrolein-indued respiratory health effects, and AR subtype-specific modulation of breathing, hemodynamic, and inflammatory responses. These results have broader translational implications, as those receiving adrenergic agonistic/antagonistic therapies might experience variable air pollution-related respiratory health effects.